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Kristina Xiao Liang's picture

Kristina Xiao Liang

Researcher, Senior Researcher
  • E-mailxiao.liang@uib.no
  • Visitor Address
    Haukeland Universitetssykehus Laboratoriebygget, 7. etg. Heis øst
    5009 Bergen
  • Postal Address
    Postboks 7804
    5020 Bergen

Mitochondrial Stem Cell Research

Main content

Human pluripotent stem cells (iPSCs) offer a unique opportunity to model human disease in a renewable and tissue-specific manner. IPSC can also be used in large-scale screening of potential therapeutic agents. Further, using new technology that allows us to correct the genetic defect in living cells, iPSC provides a potential form of treatment themselves.

The MMN group led by Prof. Laurence Bindoff is also part of the Neuro-SysMed, Center of Excellence for Clinical Research in Neurological Diseases, located in the Department of Neurology, Haukeland University Hospital. Our work with stem cells is led by senior researcher Kristina Xiao Liang as a team leader and done in close collaboration with Gareth Sullivan, University of Oslo.

We are using stem-cells transformed from the patient’s own fibroblasts to study the mitochondrial disease caused by POLG mutations. These “induced pluripotent stem cells” (iPSC) offer a unique opportunity to model human disease in a renewable and tissue-specific manner. Thus far we have successfully generated neurones and all glial cell types, cardiomyocytes, and hepatocytes from these iPSCs.

 

2022 - current: Course coordinator for the Neuro-SysMed Seminars and symposium (NEUROSYSM920), Department of Clinical Medicine (K1), University of Bergen

2021 - 2022: Course assistance for Human Physiology (OD2FYS, FARM280), Department of Biomedicine, University of Bergen

Publications:

The total number of the publications is 27, 9 with leading-corresponding authorships, 4 with co- corresponding authorships and 8 with first authorships.

  1. A Chen, CK Kristiansen, Y Hong, A Kianian, EF Fang, GJ Sullivan J Wang, X L, LA Bindoff and KX Liang (leading-corresponding author), Nicotinamide riboside and metformin ameliorate mitophagy impairment in iPSC-derived astrocytes with POLG mutations. Front. Cell Dev. Biol., 24 September 2021.
  2. KX Liang (first and leading-corresponding author), A Chen, CK Kristiansen, LA Bindoff. Flow Cytometric Analysis of Multiple Mitochondrial Parameters in Human Induced Pluripotent Stem Cells and Their Neural and Glial Derivatives. J Vis Exp. 2021 Nov 8;(177).
  3. A Chen, CK Kristiansen, LE Høyland, M Ziegler, J Wang, GJ Sullivan, X L, LA Bindoff and KX Liang (leading-corresponding author), POLG mutations lead to the abnormal mitochondria remodeling during neural differentiation of human pluripotent stem cells via inhibiting SIRT3/AMPK pathway, Cell Cycle, 21 (11), 1178-1193.
  4. CK Kristiansena, A Chen, LE Høylande, M Zieglere, GJ Sullivan, LA. Bindoff and KX Liang (leading-corresponding author), Comparing the mitochondrial signatures in ESCs and iPSCs and their neural derivations, Cell Cycle (2022), 2022 Jul 10; 1-16.
  5. KX Liang (first and leading-corresponding author), A Kianian, A Chen, CK Kristiansen, Y Hong, J Furriol, LE Høyland, M Ziegler, T Kråkenes, Cs Tzoulis, GJ Sullivan, LA. Bindoff, Stem cell derived astrocytes with POLG mutations and mitochondrial dysfunction including abnormal NAD+ metabolism is toxic for neurons. Preprint in bioRxiv (2020).
  6. Y Zhi, L Gao, B Wang, W Ren,Y Huang, KX Liang (co-corresponding author), Keqian Zhi, Ferroptosis Holds Novel Promise in Treatment of Non-coding RNA-Mediated Cancer, Front Cell Dev Biol. (2021) Jun 21;9:686906.
  7. L Zhao, J Su, S Liu, YLi, T Xi, J Ruan, KX Liang (co-corresponding author), R Huang, MAP kinase phosphatase MKP-1 regulates p-ERK1/2 signaling pathway with fluoride treatment, Biochemical and Biophysical Research Communications (2021).
  8. KX Liang (first and leading-corresponding author), GH Vatne, CK Kristiansen, O Ievglevskyi, E Kondratskaya, JC. Glover, A Chen, GJ Sullivan, LA Bindoff, N-acetylcysteine amide ameliorates mitochondrial dysfunction and reduces oxidative stress in hiPSC-derived dopaminergic neurons with POLG mutation, Experimental Neurology (2020).
  9. KX Liang (first and leading-corresponding author), CK Kristiansen, S Mostafavi, GH Vatne, GA Zanting, A Kianian, C Tzoulis, LE Høyland, M Ziegler, RM Pered, J Furriol, Z Zhang, N Balafkan, Y Hong, R Sillerg, GJ Sullivan and LA Bindoff, Disease‐specific phenotypes in iPSC‐derived neural stem cells with POLG mutations. EMBO Mol Med (2020), EMBO Mol Med 2020 Oct 7;12(10):e12146.
  10. X Liang (first and leading-corresponding author), CK Kristiansen, GH Vatne, Y Hong, LA Bindoff, Patient-specific neural progenitor cells derived from induced pluripotent stem cells offer a promise of good models for mitochondrial disease. Cell and Tissue Research (2020), 1-16.
  11. N Balafkan, S Mostafavi, M Schubert, R Siller, KX Liang, G Sullivan, LA. Bindoff, Method for differentiating human induced pluripotent stem cells toward functional cardiomyocytes in 96-well microplates, Scientific Reports (2020).
  12. L Gao, Q Wang, W Ren, J Zheng, S Li, Z Dou, X Kong, X Liang (co-corresponding author), K Zhi, The RBP1-CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma, Cell Death & Disease (2020), 11 (6), 1-16.
  13. Y Hong, X Liang, NE Gilhus, AChR antibodies show a complex interaction with human skeletal muscle cells in a transcriptomic study, Scientific Reports (2020), 10 (1), 1-13.
  14. Z Zhang, Z Gao, S Rajthala, D Sapkota, H Dongre, H Parajuli, S Suliman, R Das, L Li, LA Bindoff, DE Costea, X Liang (leading-corresponding author), Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma, Cellular and Molecular Life Sciences (2019), 1- 19.
  15. L Gao, ZC Dou, WH Ren, SM Li, X Liang (co-corresponding author), KQ Zhi, CircCDR1 as upregulates autophagy under hypoxia to promote tumor cell survival via AKT/ERK 1⁄2/mTOR signaling pathways in oral squamous cell carcinomas, Cell Death & Disease (2019), 10 (10), 1-16.
  16. Z Zhang, X Liang, Y Fan, Z Gao, LA Bindoff, DE Costea, L Li, Fibroblasts rescue oral squamous cancer cell from metformin-induced apoptosis via alleviating metabolic disbalance and inhibiting AMPK pathway. Cell Cycle (2019), 18 (9), 949-962.
  17. Q Wang, Y Zhi, W Ren, S Li, Z Dou, X Xing, X Quan, Y Wang, C Jiang, X Liang, L Gao, K Zhi, Suppression of OSCC malignancy by oral glands derived-PIP identified by iTRAQ combined with 2D LC-MS/MS, Journal of Cellular Physiology (2019), 234 (9), 15330-15341
  18. K Kitajima, R Das, X Liang, E Neppelberg, AC Johannessen, DE Costea, et al, AChR antibodies show a complex interaction with human skeletal muscle cells in a transcriptomic study, Odontology (2019), 107 (3), 291- 300.
  19. X Liang, Z Wei, D Hu, J Ruan. Prevalence of dentin hypersensitivity among the residents of Xi'an city, China, Acta Odontol Scand (2017), Aug;75(6):387-393.
  20. A Biddle, L Gammon, X Liang, DE Costea, IC Mackenzie, Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell, EBioMedicine (2016); 4: 138-45.
  21. N Yang, T Yan, H Zhu, Liang X, L Leiss, PØ Sakariassen, KO Skaftnesmo, B Huang, DE Costea, PØ Enger, X Li, J.J Wang, A co-culture model with brain tumorspecific bioluminescence demonstrates astrocyte- induced drug resistance in glioblastoma, Transl Med. (2014), Oct 4;12:278.
  22. X Liang, KA Graham, AC Johannessen, DE Costea, FH Labeed, Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance, Integrative Biology (2014), 6 (5), 545- 554.
  23. X Liang, T Osman, D Sapkota, E Neppelberg, S Lybak, PG Liavaag, et al., Rapid adherence to collagen IV enriches for tumour initiating cells in oral cancer, European Journal of Cancer (2014), 50 (18), 3262-3270.
  24. N Yang, H Zhu, T Yan, X Liang, LW Leiss, PØ Enger, X Li, J Wang, A novel model to study the stroma-induced drug resistance in glioblastoma cells, Cancer Research (2014), 74 (19 Supplement).
  25. A Biddle, X Liang, L Gammon, B Fazil, LJ Harper, H Emich, DE Costea, Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative, Cancer Research (2011), 71 (15), 5317-5326.
  26. HJ Mulhall, R Abdallat, X Liang, S Fedele, MP Lewis, S Porter, et al., Rapid detection of oral cancer: Electrophysiological characterization by electrophoresis technology, TechConnect Briefs, Volume: 3, Nanotechnology (2010): Bio Sensors, Instruments, Medical, Environment and Energy (2010).
  27. K Que, J Ruan, X Fan, X Liang, D Hu, A multi-centre and cross-sectional study of dentine hypersensitivity in China, J Clin Periodontal (2010), Jul;37(7):631-7.
  • Show author(s) (2022). POLG mutations lead to abnormal mitochondrial remodeling during neural differentiation of human pluripotent stem cells via SIRT3/AMPK pathway inhibition. Cell Cycle. 1178-1193.
  • Show author(s) (2022). MiR-152-5p suppresses osteogenic differentiation of mandible mesenchymal stem cells by regulating ATG14-mediated autophagy. Stem Cell Research & Therapy.
  • Show author(s) (2022). Comparing the mitochondrial signatures in ESCs and iPSCs and their neural derivations. Cell Cycle. 2206-2221.
  • Show author(s) (2021). Nicotinamide riboside and metformin ameliorate mitophagy defect in induced pluripotent stem cell-derived astrocytes with POLG mutations. Frontiers in Cell and Developmental Biology. 1-20.
  • Show author(s) (2021). MAP kinase phosphatase MKP-1 regulates p-ERK1/2 signaling pathway with fluoride treatment. Biochemical and Biophysical Research Communications - BBRC. 65-72.
  • Show author(s) (2021). Flow cytometric analysis of multiple mitochondrial parameters in human induced pluripotent stem cells and their neural and glial derivatives. Journal of Visualized Experiments.
  • Show author(s) (2021). Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs. Frontiers in Cell and Developmental Biology. 1-14.
  • Show author(s) (2020). The RBP1–CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma. Cell Death & Disease. 1-16.
  • Show author(s) (2020). Patient-specific neural progenitor cells derived from induced pluripotent stem cells offer a promise of good models for mitochondrial disease. Cell and Tissue Research. 15-30.
  • Show author(s) (2020). N-acetylcysteine amide ameliorates mitochondrial dysfunction and reduces oxidative stress in hiPSC-derived dopaminergic neurons with POLG mutation. Experimental Neurology.
  • Show author(s) (2020). Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations. EMBO Molecular Medicine. 1-26.
  • Show author(s) (2020). AChR antibodies show a complex interaction with human skeletal muscle cells in a transcriptomic study. Scientific Reports. 13 pages.
  • Show author(s) (2020). A method for differentiating human induced pluripotent stem cells toward functional cardiomyocytes in 96‐well microplates. Scientific Reports. 1-14.
  • Show author(s) (2019). Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts. Cellular and Molecular Life Sciences (CMLS). 1-19.
  • Show author(s) (2018). W748S POLG mutation induced mitochondrial changes in hiPSC-differentiated NSCs.
  • Show author(s) (2018). Isolation and characterization of cells derived from human epithelial rests of Malassez. Odontology : official journal of The Society of the Nippon Dental University. 1-10.
  • Show author(s) (2017). Prevalence of dentin hypersensitivity among the residents of Xi'an city, China. Acta Odontologica Scandinavica. 387-393.
  • Show author(s) (2016). Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma. EBioMedicine. 138-145.
  • Show author(s) (2014). Rapid adherence to collagen IV enriches for tumour initiating cells in oral cancer. European Journal of Cancer. 3262-3270.
  • Show author(s) (2014). Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance. Integrative Biology. 545-554.
  • Show author(s) (2014). Carcinoma-associated fibroblasts promote a cancer stem cell-like phenotype.
  • Show author(s) (2014). A co-culture model with brain tumor-specific bioluminescence demonstrates astrocytes-induced drug resistance in glioblastoma. Journal of Translational Medicine.
  • Show author(s) (2013). Biological Characteristics of Stem-Like Cells in Oral Squamous Cell Carcinoma.

More information in national current research information system (CRIStin)

  Multiple iPSC-based in vitro model systems.

  • 2D: neural stem cells, DA neurons, motor neurons, generic neurons, astrocytes, oligodendrocytes and cardiomyocytes.
  • 3D: mini-brain organoid system
  • Co-culture systems

  Modeling diseases using neural stem cells, neurons, astrocytes, and astrocyte-neurons interactions.

  Developing a high-throughput iPSC-based platform for screening the therapeutic agents.

  Investigating metabolic reprogramming between the neurons and glial cells

  Using single-cell transcriptomics for multidimensional phenotyping.